The invention relates to porous polymer matrices.
Porous polymer media, such as membranes, macroporous solids, and cellular solids are used in a wide variety of applications. These materials are used as support structures for gas and solution phase catalysis; support structures for solid phase synthesis; immobilized beds in bioreactors; and thermal insulation.
Recent advances in the field of tissue engineering have led to new uses for these porous materials. Tissue engineering techniques provide alternatives to the prosthetic materials currently used in plastic and reconstructive surgery, and in joint repair and replacement; these techniques are also useful in the formation of organ equivalents to replace diseased, defective, or injured organs. Porous materials are used as scaffolds for the in vitro or in vivo growth and development of tissue. Because these materials are placed in the human body, they must often have structural and functional characteristics that differ from the requirements for materials used in non-therapeutic applications.
The invention features porous matrices that are useful in a variety of applications, including tissue engineering, electromagnetic shielding, and fuel cell applications.
In a first aspect, the invention features a matrix including a macrostructure having a semi-solid network and voids; the matrix further includes a microstructure, which preferably has voids; the microstructure is located within the semi-solid network. In a preferred matrix, the semi-solid network includes a polymer or a copolymer. The copolymer can have a carboxylic acid group or an amine group. Another preferred matrix includes a conductive polymer selected from the group consisting of polypyrrole, polyaniline, polyacetylene, and polythiophene.
In a preferred matrix, the semi-solid network consists essentially of a polymer or mixture of polymers. In another preferred matrix, the semi-solid network is substantially continuous.
The voids of the macrostructure can also be substantially continuous. The voids of the macrostructure and the voids of the microstructure can be connected or not connected. The voids of the macrostructure define openings. In a preferred matrix, the average diameter of the openings and the average diameter of the cross-sections of the semi-solid network have a ratio of from 2:1 to 10:1, and more preferably have a ratio of from 2:1 to 5:1.
In a preferred embodiment, a cubic matrix having dimensions of about 0.5 cm on all sides and having voids defining openings with an average diameter of 50-500 xcexcm has a connectivity number of at least 10, and more preferably has a connectivity number of at least 20.
A ratio of the maximum diameter and the minimum diameter of a cross section of the semi-solid network of a preferred matrix is from 1:1 to 10:1, and more preferably is from 1:1 to 4:1, or from 1:1 to 2:1.
In another preferred matrix, at least 10% of the voids of the microstructure have a fractal dimension of at least 3; preferably, less than 10% of the voids of the macrostructure of this matrix have a fractal dimension higher than 1. A preferred matrix is three dimensional, and the exterior face of the matrix can be porous.
The matrix can include an additive, at least 5% of which is located within the microstructure; the preferred additive is selected from the group consisting of transition metal oxides, transition metal sulfates, transition metal carbonates, transition metal phosphates, transition metal nitrates, sodium carbonate, sodium phosphate, calcium carbonate, calcium phosphate, xcex2-glycerophosphate, and hydroxyapatite having particle sizes of greater than 150 xcexcm. The additive can also be selected from the group consisting of polyethylene fibers, polypropylene fibers, Teflon(copyright) (polytetrafluoroethylene) fibers, nylon fibers, and PGA fibers; it can also be selected from the group consisting of titanium fibers, titanium powder, and titanium dioxide; or from the group consisting of inorganic and organic reducing agents.
A preferred matrix has a porosity of at least about 20%, and more preferably has a porosity of at least about 40%, 70%, 90%, 92%, or 95%. A preferred matrix is biodegradable, bioerodible, or bioresorbable. The matrix can be permeable or impermeable to cells; it is preferably permeable to bodily fluids. A preferred matrix includes a living cell; preferably, the cell is selected from the group consisting of bone marrow cells, periosteal cells, chondrocytes, smooth muscle cells, endothelial cells, fibroblasts, epithelial cells, tenocytes, neuronal cells, Schwann cells, hepatocytes, Kupffer cells, fibroblasts, pancreatic islet cells, and cardiac myocytes. Another preferred matrix includes a bioactive agent, which is preferably contained in microspheres. The bioactive agent is selected from the group consisting of antibiotics, anesthetics, anti-inflammatory agents, contrast agents, and imaging agents.
A preferred matrix has a coating; less than 5% of the coating is contained in the voids of the microstructure. The coating may be attached to the matrix by electrostatic forces, by covalent bonding, or as a result of the shape of the coating. In this last case, the coating encases at least a portion of the matrix.
The matrix may be coated by any coating known to those skilled in the art to be appropriate, however, another preferred matrix is coated with a hydrophilic material selected from the group consisting of collagen, PEG, PEO, PVA, hydrogels, carboxylic acid-containing substances, fibronectin, vitronectin, laminin, and bone morphogenetic protein (BMP).
Yet another preferred matrix includes bioerodible fibers; the fibers preferably include PGA or therapeutic agents. Another preferred matrix includes a protein that is protected with a cyclodextrin.
A preferred matrix changes in size less than 50% when cells are added to the matrix; another preferred matrix has a compressive modulus which is higher than known polymer matrices having the same components in the same ratio. For example, a preferred matrix has a compressive modulus of at least 0.4 MPa at 4% strain. In addition, a preferred matrix is non-friable.
In a second aspect, the invention features a porous polymer matrix that changes in size less than 50% when cells are added to the matrix. A preferred matrix changes in size less than 25% when cells are added to the matrix, and more preferably changes in size less than 10%. In a preferred embodiment the change in matrix size is defined as that change which occurs over a limited time period, of over a period of less than xc2xd the time it takes for the matrix to degrade, preferably, less than {fraction (1/10)} the time it takes for the matrix to degrade, most preferably, the period of time during which the initial cells are added to the matrix if such time is less than {fraction (1/10)} the time it takes for the matrix to degrade.
A preferred matrix has a macrostructure having a semi-solid network and voids and a microstructure having voids; the microstructure is located within the semi-solid network. Preferably, the voids of the macrostructure are substantially continuous. A preferred matrix has a porosity of at least 90%, and more preferably has a porosity of at least 92%, or 95%. A preferred matrix is biodegradable, bioerodible or bioresorbable. A preferred matrix is permeable to bodily fluids. Another preferred matrix includes a living cell or a bioactive agent.
A preferred matrix has a coating; less than 5% of the coating is contained in the voids of the microstructure. The coating may be attached to the matrix by electrostatic forces, by covalent bonding, or as a result of the shape of the coating. In this last case, the coating encases at least a portion of the matrix.
The matrix may be coated with any suitable coating known to those skilled in the art, another preferred matrix is coated with a hydrophilic material selected from the group consisting of collagen, PEG, PEO, PVA, hydrogels, carboxylic acid-containing substances, fibronectin, vitronectin, laminin, and bone morphogenetic protein (BMP).
A preferred matrix is three dimensional. The exterior face of a preferred matrix is porous. Another preferred matrix includes an additive; at least 5% of the additive is located within the microstructure. A preferred matrix has a density of less than about 0.150 g/cc, and more preferably has a density of less than about 0.120 g/cc.
In a third aspect, the invention features a porous polymer matrix including poly(lactic acid) and/or poly(lactic acid-co-glycolic acid), and at least one hydrophilic polymer selected from the group consisting of poly(ethylene glycol), poly(ethylene oxide), polypropylene oxide, polypropylene glycol, poly(vinyl alcohol), a copolymer of polypropylene oxide and polyethylene oxide, collagen, gelatin, fibronectin, glycosaminoglycan, and polylysine. The poly(ethylene glycol) preferably has ester linkages. A preferred matrix includes a blend of poly(lactic acid), preferably poly(L-lactic acid), and poly(lactic acid-co-glycolic acid).
A preferred matrix includes at least 0.1% of the hydrophilic polymer, and more preferably includes at least 1% of the hydrophilic polymer, at least 5% of the hydrophilic polymer, at least 10% of the hydrophilic polymer, or at least 20% of the hydrophilic polymer.
Preferably, the matrix includes at least one additive selected from the group consisting of calcium carbonate, xcex2-glycerophosphate, calcium phosphate, sodium phosphate, sodium carbonate, sodium bicarbonate, and sodium chloride.
A preferred matrix includes calcium carbonate having particle sizes ranging from 5 xcexcm to 500 xcexcm. Preferably, the matrix includes 50-100% by weight of calcium carbonate, relative to the weight of poly(lactic acid) or poly(lactic acid-co-glycolic acid), or to the combined weight of poly(lactic acid) and poly(lactic acid-co-glycolic acid), if the matrix includes both of these polymers.
Another preferred matrix includes xcex2-glycerophosphate having particle sizes ranging from 5 xcexcm to 500 xcexcm. Preferably the matrix includes 50-100% by weight of xcex2-glycerophosphate, relative to the weight of poly(lactic acid) or poly(lactic acid-co-glycolic acid), or to the combined weight of poly(lactic acid) and poly(lactic acid-co-glycolic acid), if the matrix includes both of these polymers.
Another preferred matrix includes hydroxyapatite having particle sizes of at least 150 xcexcm. The matrix preferably includes between 5 and 150% by weight of hydroxyapatite, relative to the weight of the polymer.
A preferred matrix has a macrostructure having a semi-solid network and voids; the matrix further includes a microstructure having voids; the microstructure is located within the semi-solid network. A preferred matrix has a porosity of at least about 90%. Another preferred matrix includes a living cell or a bioactive agent. A preferred matrix is three dimensional. Preferably, the exterior face of the matrix is porous.
A preferred matrix includes an additive; at least 5% of the additive is located within the microstructure. Preferably, the matrix changes in size less than 50% when cells are added to the matrix. A preferred matrix has a density of less than about 0.150 g/cc, and more preferably has a density of less than about 0.120 g/cc.
In a fourth aspect, the invention features a porous matrix consisting essentially of a polymer, or a mixture of polymers, where the matrix has a compressive modulus which is higher than known polymer matrices having the same components in the same ratio. For example, a preferred matrix has a compressive modulus of at least 0.4 MPa at 4% strain. Preferably, the matrix has a porosity of at least about 90%. A preferred matrix is biodegradable, bioerodible, or bioresorbable. Preferably, the matrix includes a living cell or a bioactive agent.
A preferred matrix has a coating; less than 5% of the coating is contained in the voids of the microstructure. The coating may be attached to the matrix by electrostatic forces, by covalent bonding, or as a result of the shape of the coating. In this last case, the coating encases at least a portion of the matrix.
While the matrix may be coated with any suitable coating known to those skilled in the art, another preferred matrix is coated with a hydrophilic material selected from the group consisting of collagen, PEG, PEO, PVA, hydrogels, carboxylic acid-containing substances, fibronectin, vitronectin, laminin, and bone morphogenetic protein (BMP).
A preferred matrix is substantially free of hydroxyapatite. A preferred matrix is three dimensional. Preferably, the exterior face of the matrix is porous. A preferred matrix includes an additive; at least 5% of the additive is located within the microstructure. A preferred matrix changes in size less than 50% when cells are added to the matrix. A preferred matrix has a density of less than about 0.150 g/cc, and more preferably has a density of less than about 0.120 g/cc.
In a fifth aspect, the invention features a matrix having a porosity of at least 90%. A preferred matrix is biodegradable, bioerodible, or bioresorbable. Preferably, the matrix includes a living cell or a bioactive agent.
A preferred matrix has a coating; less than 5% of the coating is contained in the voids of the microstructure. The coating may be attached to the matrix by electrostatic forces, by covalent bonding, or as a result of the shape of the coating. In this last case, the coating encases at least a portion of the matrix.
Another preferred matrix is coated with a hydrophilic material selected from the group consisting of collagen, PEG, PEO, PVA, hydrogels, carboxylic acid-containing substances, fibronectin, vitronectin, laminin, and bone morphogenetic protein (BMP). Preferably, the matrix is substantially free of hydroxyapatite. A preferred matrix is three dimensional. Preferably, the matrix changes in size less than 50% when cells are added to the matrix.
In a sixth aspect, the invention features a porous polymer matrix that bioerodes at substantially the same rate that cells populate the matrix. A preferred matrix has a porosity of at least about 90%. Preferably, the matrix includes a bioactive agent.
A preferred matrix has a coating; less than 5% of the coating is contained in the voids of the microstructure. The coating may be attached to the matrix by electrostatic forces, by covalent bonding, or as a result of the shape of the coating. In this last case, the coating encases at least a portion of the matrix.
Another preferred matrix is coated with a hydrophilic material selected from the group consisting of collagen, PEG, PEO, PVA, hydrogels, carboxylic acid-containing substances, fibronectin, vitronectin, laminin, and bone morphogenetic protein (BMP).
A preferred matrix changes in size less than 50% when cells are added to the matrix. Preferably, the matrix has a compressive modulus which is higher than known polymer matrices having the same components in the same ratio. For example, a preferred matrix has a compressive modulus of at least 0.4 MPa at 4% strain.
In a seventh aspect, the invention features a porous polymer matrix that bioerodes at substantially the same rate that tissue ingrows into the matrix.
In an eighth aspect, the invention features a porous polymer matrix that bioerodes at substantially the same rate that tissue remodeling occurs within the matrix.
In a ninth aspect, the invention features a composition including two layers, each layer including a matrix having voids, where the first layer has voids with an average size of less than 50 xcexcm, and the second layer has voids with an average size of greater than 100 xcexcm.
In a tenth aspect, the invention features a porous polymeric fiber. Preferably, the fiber includes a macrostructure having a semi-solid network and voids and a microstructure having voids, where the microstructure is located within the semi-solid network. In a preferred fiber, the voids are elongated and oriented in the same direction. Preferably, the fiber includes a bioactive agent.
In an eleventh aspect, the invention features a polymer matrix including an additive selected from the group consisting of transition metal oxides, transition metal sulfates, transition metal carbonates, transition metal phosphates, transition metal nitrates, sodium carbonate, sodium phosphate, calcium carbonate, calcium phosphate, xcex2-glycerophosphate, and hydroxyapatite having particle sizes of greater than 150 xcexcm.
In a twelfth aspect, the invention features a method of making a porous polymer matrix using a composition including a solvent, a porogen, and a polymer, where at least 50%, and more preferably at least 80%, or at least 90% of the solvent and the porogen are recovered. Preferably, the porogen is biodegradable.
In a thirteenth aspect, the invention features a method of making a porous polymer matrix. The method includes (a) combining a polymer solution and a porogen to form a mixture, and (b) extracting the porogen from the mixture and precipitating the polymer substantially simultaneously. The step of combining the polymer solution and the porogen can include depositing the polymer solution around the porogen using a three-dimensional printing technique. Preferably, the matrix is bounded on all sides during step (b). Preferably, the porogen is cryo-milled prior to step (a). The solvent is preferably removed by lyophilization. In a preferred method, a protein stabilized with a cyclodextrin is combined with the polymer and the porogen in step (a).
In a fourteenth aspect, the invention features a method of making a porous polymer matrix. The method includes (a) combining a polymer solution and an irregularly shaped porogen to form a mixture; and (b) extracting the porogen from the mixture.
In a fifteenth aspect, the invention features a method of making a porous polymer matrix; the method includes (a) combining a polymer solution and a porogen that has been cryo-milled to form a mixture; and (b) extracting the porogen from the mixture.
In a sixteenth aspect, the invention features a composition consisting essentially of irregularly shaped and sized wax particles. Preferably, at least 90% of the wax particles are smaller than 5000 xcexcm.
In a seventeenth aspect, the invention features a method of making wax particles that includes cryo-milling wax. The invention further features a composition consisting essentially of a plurality of wax particles that are formed by cryo-milling wax. The invention also features a porous matrix including voids, where at least 10% of the voids in the matrix are made using this composition.
In an eighteenth aspect, the invention features a method of making wax particles; the method includes spraying the wax in a liquid solution or a liquid form into a coolant. The invention also features a composition consisting essentially of a plurality of wax particles formed by this method. The invention further features a porous matrix including voids, where at least 10% of the voids in the matrix are made using this composition.
In a nineteenth aspect, the invention features a method for controlling the mechanical strength of a porous polymer matrix that includes a water insoluble polymer and a water soluble polymer; the mechanical strength of the matrix may be optimized by alterations in the ratio of the water insoluble polymer and the water soluble polymer. Preferably, the porosity of the matrix remains substantially unchanged.
In a twentieth aspect, the invention features a method for controlling the degradation rate of a porous polymer matrix that includes a water insoluble polymer and a water soluble polymer; the method includes altering the ratio of the water insoluble polymer and the water soluble polymer. Preferably, the porosity of the matrix remains substantially unchanged.
In a twenty-first aspect, the invention features a mold for shaping an object; the mold has a plurality of sides, each of which defines a plurality of openings; at least two of the sides are permanently joined, and at least one side is detachable. Preferably, the mold includes Teflon(copyright) (polytetrafluoroethylene).
In a twenty-second aspect, the invention features a method for preparing a three dimensional porous polymer matrix including the steps of: (a) preparing a polymer solution; (b) adding particles with a size of less than 5000 xcexcm to the polymer solution that are insoluble or sparingly soluble in the polymer solvent at the temperature of the polymer solution when the particles are added; (c) mixing the solid particles and the solution to form a polymer/particle mixture; and (d) extracting the particles from the polymer/particle mixture with a solvent that is a solvent for the particles and a non-solvent for the polymer. In preferred embodiments: the polymer/particle mixture has a consistency between that of a viscous liquid and that of a paste; the method further includes molding or extruding the polymer/particle mixture before the particles are extracted; the method further includes removing the remaining solvent by evaporation; or the polymer is a water-soluble polymer, such as collagen, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, polyethylene oxide-polypropylene oxide copolymer, polyvinyl pyrrolidone, protein, peptide, or cellulose.
In another preferred embodiment, the polymer is a water-insoluble polymer, and can be selected from the group consisting of polyesters, poly(ester amides), polyamides, polyanhydrides, polyorthoesters, polycarbonates, polyurethanes, polyethers and poly(ether esters). In another preferred embodiment, the particles are made from a material selected from the group consisting of natural waxes, synthetic waxes and wax-like polymers; the particles can also be selected from the group consisting of paraffin, beeswax, and low density polyethylene. The size of the particles is preferably between about 50 and 500 xcexcm.
In preferred embodiments, the polymer/particle mixture includes a component selected from the group consisting of industrial catalysts, diagnostic agents and therapeutic agents. The therapeutic agents can be selected from the group consisting of cells, osteoinductive materials and osteoconductive materials.
In a twenty-third aspect, the invention features a porous polymer matrix prepared by: (a) preparing a polymer solution; (b) adding to the solution an effective amount of solid particles with a size of less than 5000 xcexcm that are insoluble or sparingly soluble in the polymer solvent at the temperature of the polymer solution when the particles are added; (c) mixing the solid particles and the solution to form a polymer/particle mixture; and (d) extracting the particles from the polymer/particle mixture with a solvent that is a solvent for the particles and a non-solvent for the polymer while simultaneously precipitating the polymer. Preferably, the polymer/particle mixture has a consistency between that of a viscous liquid and that of a paste. A preferred matrix is made by molding or extruding the polymer/particle mixture before the particles are extracted.
The polymer can be a water-soluble polymer, and can be selected from the group consisting of collagens, polyethylene glycols, polyethylene oxides, polyvinyl alcohols, polyethylene oxide-polypropylene oxide copolymers, polyvinyl pyrrolidones, proteins, peptides, and celluloses. In other embodiments, the polymer is a water-insoluble polymer, and can be selected from the group consisting of polyesters, poly(ester amides), polyamides, polyanhydrides, polyorthoesters, polycarbonates, polyurethanes, polyethers and poly(ether esters).
The particles can be particles of natural waxes, synthetic waxes and wax-like polymers. The waxes and wax-like polymers can be selected from the group consisting of paraffin, beeswax, and low density polyethylene. In other embodiments, the particles are polymer particles. Preferably the size of the particles is between about 50 and 500 xcexcm.
In other preferred embodiments, the polymer/particle mixture includes a component selected from the group consisting of industrial catalysts, diagnostic agents, therapeutic agents. The therapeutic agent can be selected from the group consisting of cells, osteoinductive materials, and osteoconductive materials.
The matrix can be formed into the shape of a hollow tube; formed into a solid object selected from the group consisting of rods, pins, screws, plates and anatomical shapes; formed into a solid object selected from the group consisting of porous electrodes, porous fibers, and porous solid support materials; or formed into particles suitable for pulmonary delivery or injection.
In a twenty-fourth aspect, the invention features a polymer matrix with a porosity between about 10 and 95% which is substantially uniform throughout the matrix, prepared by (a) dissolving a water-soluble polymer in a solution; (b) adding particles with a size of less than 5000 xcexcm to the polymer solution that are insoluble or sparingly soluble in the polymer solvent at the temperature of the polymer solution when the particles are added; (c) mixing the solid particles and the solution to form a polymer/particle mixture; and (d) extracting the particles from the polymer/particle mixture with a solvent that is a solvent for the particles and a non-solvent for the polymer.
xe2x80x9cPorous polymer matrixxe2x80x9d means any solid object made of a polymer, which forms a continuous or discontinuous porous network. Porous polymer matrices include porous membranes, porous foams, and porous beads.
xe2x80x9cMacrostructure,xe2x80x9d as used herein when referring to a matrix, means the semi-solid network of the matrix and the continuous voids defined by the network.
xe2x80x9cMicrostructure,xe2x80x9d as used herein when referring to a matrix, means the system of voids that are contained within the semi-solid network of the matrix.
xe2x80x9cSemi-solid,xe2x80x9d as used herein when referring to a structure, means that the structure can have voids.
xe2x80x9cVoidsxe2x80x9d mean portions of a matrix that do not contain the material that makes up the semi-solid network of the matrix; the voids are filled with any substance that is different from the substance that makes up the majority of the semi-solid network.
The xe2x80x9cdiameter of a voidxe2x80x9d means the diameter of the largest sphere that would fit through the opening defined by the void.
xe2x80x9cConnectivity numberxe2x80x9d means the number of cuts that must be made in order to ensure that an object is separated into at least two completely separate pieces.
A xe2x80x9ccutxe2x80x9d means a cut that passes through a meridional circle of the semi-solid network and does not pass through a void of the matrix.
A xe2x80x9ccross-sectionxe2x80x9d means a section that can be drawn through a portion of the semi-solid network of the matrix by drawing a meridional curve on the exterior surface of the portion.
A xe2x80x9cminimum diameter of a cross sectionxe2x80x9d means the shortest straight line that can be drawn that joins two edges of the cross-section and passes through the center of the cross-section.
A xe2x80x9cmaximum diameter of a cross sectionxe2x80x9d means the longest straight line that can be drawn that joins two edges of the cross-section.
A xe2x80x9cdiameter of a cross-sectionxe2x80x9d is the mean of the minimum and maximum diameters.
xe2x80x9cAverage diameter of the cross sections of the semi-solid network,xe2x80x9d means the mean of the diameters of the cross sections of the semi-solid network.
xe2x80x9cContinuous,xe2x80x9d as used herein when referring to the semi-solid network, means that the relevant portions of the semi-solid network are joined as one piece. That is, a line can be drawn from one point on the surface to another point without leaving the surface of the semi-solid network and without crossing a void. Similarly, continuous, as used herein when referring to voids, means that a line can be drawn connecting a point in the void space with another point in the void space, without leaving the void space and without crossing the semi-solid network.
xe2x80x9cFractal,xe2x80x9d as used herein, means an irregular curve or shape that repeats itself over a continuous surface at different scales.
An xe2x80x9cexterior face of the matrixxe2x80x9d means the face that is adjacent to the mold during formation of the matrix.
xe2x80x9cPorogen,xe2x80x9d as used herein, means a non-gaseous material that is soluble in at least one solvent and sparingly soluble in at least one solvent, that is combined with a material to form a mixture, then removed from the mixture to leave voids.
xe2x80x9cSparingly solublexe2x80x9d describes a material that, under the conditions of processing, has a solubility of less than 30% by weight in the given solvent, and preferably has a solubility of less than 20% by weight, less than 10% by weight, or less than 2% by weight.
xe2x80x9cNon-solvent,xe2x80x9d as used herein, describes a solvent in which a given material is insoluble or sparingly soluble.
xe2x80x9cHydrophilicxe2x80x9d describes a material that has a solubility of at least 0.5% by weight in water.
xe2x80x9cMicrospheresxe2x80x9d describe objects having an average diameter of about 2 xcexcm to about 100 xcexcum. They are composed of synthetic polymers, biological polymers, or blends or combinations thereof.
xe2x80x9cBioactive agentxe2x80x9d describes a substance that has a physiological or biological effect on a cell, tissue, organ, or other living structure.
xe2x80x9cBiodegradablexe2x80x9d means capable of being broken down into innocuous products when placed within a living system, such as a cell culture system, or a living organism, such as a human or animal, or when exposed to bodily fluids.
xe2x80x9cBioerodiblexe2x80x9d means capable of being dissolved or suspended in biological fluids.
xe2x80x9cBioresorbablexe2x80x9d means capable of being absorbed by the cells, tissue, or fluid in a living body.
xe2x80x9cBioerodes at substantially the same rate that cells populatexe2x80x9d means that an object, such as a matrix, bioerodesxe2x80x94that is, is dissolved or suspended in biological fluidsxe2x80x94at the same rate that cells grow and produce extracellular matrix (ECM), so that the total volume of the matrix material, the cells, and the ECM within the matrix remains substantially constant.
xe2x80x9cSubstantially constant,xe2x80x9d when referring to the total volume of the matrix material, the cells, and the extracellular matrix within the matrix, means a change in the total volume of less than 25%, and preferably less than 15%, or 5%. xe2x80x9cImpermeable,xe2x80x9d as used herein, means that cells can migrate into the material to a depth of less than 200 xcexcm. xe2x80x9cThree-dimensional,xe2x80x9d as used herein, means that the smallest dimension of an object (e.g., length, width, or depth) is at least 100 xcexcm.
xe2x80x9cNon-friablexe2x80x9d means that when cut, the portions separate into masses with a total loss of materials to flaking or powdering being less than 5% of the total mass of the material.
The matrices of the invention offer several advantages over existing matrices. The porous nature of the matrices and the high surface areas provide an environment that is permissive to cell ingrowth. In addition, the highly interconnected structure of the matrices provides them with mechanical strength.
The methods of the invention provide convenient, cost-effective ways to prepare porous polymer matrices. In addition, the methods of the invention provide novel ways to alter physical properties of the matrices.